Real-World, First-Line IO-Based Combos Are Associated With Improved OS vs TKI Monotherapy in Advanced RCC

First-line immuno-oncology (IO)–based combination regimens, particularly IO plus a TKI, were associated with improved overall survival (OS) compared with TKI monotherapy in a real-world cohort of patients with advanced renal cell carcinoma (RCC), according to findings from a retrospective real-world study presented at the 2026 Kidney Cancer Research Summit.^1,2

Findings showed that at a median follow-up of 13.9 months, the median OS in the overall population (n = 2123) was 34.7 months.¹ Notably, the median OS was 44.1 months among patients who received an IO-TKI combination (n = 987) compared with 32.8 months for those given an IO-IO combination (n = 746) and 29.8 months for patients given TKI monotherapy (n = 390).

Notably, from 2019 to 2024, the proportion of patients receiving an IO-TKI combination increased from 33.8% to 48.6%, whereas IO-IO decreased from 40.5% to 34.5% and TKI monotherapy decreased from 25.7% to 16.9%.

“The advanced RCC treatment landscape continues to evolve toward IO-based combinations in [the] first line and continued TKI monotherapy in later lines,” lead study author Neil J. Shah, MBBS, and colleagues wrote in the poster. “While health care resource utilization [HCRU] and costs remain substantial, these results underscore both the clinical progress achieved and the ongoing opportunity to optimize resource use in advanced RCC care.”

Shah is an assistant attending physician and genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York.

How was the real-world advanced RCC analysis conducted?

Investigators conducted a retrospective cohort study using Optum’s deidentified Clinformatics Data Mart Database, with the database period extended from January 1, 2017, through December 31, 2024, and included commercially insured and Medicare Advantage beneficiaries.

Eligible adults had at least 2 claims with an RCC diagnosis, evidence of secondary metastasis, and initiation of a National Comprehensive Cancer Network–recommended first-line systemic regimen on or after April 19, 2019. Patients were categorized according to whether they received IO-TKI, IO-IO, or TKI monotherapy.

Investigators evaluated outcomes included treatment patterns, treatment sequencing, OS, all-cause and advanced RCC–related HCRU, and costs. OS was estimated using an unadjusted Kaplan-Meier analysis, and HCRU and costs were calculated on a per-patient-per-month (PPPM) basis.

What were the patient characteristics?

The mean age of the overall population was 68.1 years (standard deviation [SD], 9.6), and the median age was 69.0 years (interquartile range [IQR], 63.0-75.0). The respective mean ages were 67.4, 68.2, and 69.5 years in the IO-TKI, IO-IO, and TKI monotherapy groups. Men comprised 70.9% of the overall population, including 71.6%, 72.8%, and 65.6% of the respective treatment cohorts.

Overall, 50.2% of patients were non-Hispanic White, 7.3% were non-Hispanic Black, 13.6% were Hispanic, and 2.2% were Asian; race or ethnicity was unknown for 26.7% of patients. Most patients lived in the South (45.1%), followed by the Midwest (25.1%), West (19.5%), and Northeast (10.3%).

Medicare Advantage covered 71.1% of the study population, and 28.9% had commercial insurance. The proportion covered by Medicare Advantage was highest in the TKI-monotherapy group at 78.7%, compared with 71.0% in the IO-IO group and 68.1% in the IO-TKI group.

What other treatment patterns and survival outcomes were observed?

Additional data showed that 32.3% of patients remained on their initial treatment, 29.0% advanced to second-line therapy, and 18.7% died. Another 20.0% discontinued treatment without a recorded death or subsequent therapy.

TKI monotherapy was the most frequently used treatment class in both the second- and third-line settings. Among patients who received second-line therapy, 47.2% received TKI monotherapy compared with 23.1% who received IO-TKI, 9.3% who received IO monotherapy, 7.6% who received a TKI plus an mTOR inhibitor, 7.0% who received IO-IO, and 5.8% who received another regimen.

In the third-line setting, 42.1% of patients received TKI monotherapy, 18.8% received IO-TKI, and 14.2% received a TKI plus an mTOR inhibitor; other treatments were administered to 15.2% of patients.

What were the HCRU and cost findings?

Overall, 61.3% of patients had at least 1 inpatient admission, including 57.6% treated with first-line IO-TKI, 66.6% treated with IO-IO, and 60.5% treated with TKI monotherapy. The median PPPM inpatient admissions was 0.1 overall. Median lengths of stay were 1.0 day with IO-TKI, 1.1 days with IO-IO, and 1.3 days with TKI monotherapy.

At least 1 emergency department visit was reported for 64.1% of patients, whereas 99.8% had at least 1 outpatient visit. The median number of outpatient visits PPPM was 5.4 overall, including 5.5 with IO-TKI, 5.6 with IO-IO, and 4.3 with TKI monotherapy.

Median total health care costs PPPM were $32,829 overall, $38,408 with IO-TKI, $30,484 with IO-IO, and $24,098 with TKI monotherapy.

Median medical costs PPPM were highest with IO-IO at $26,589, compared with $21,800 for IO-TKI and $7462 for TKI monotherapy. Conversely, median pharmacy costs were $15,871 with IO-TKI, $15,103 with TKI monotherapy, and $415 with IO-IO. Investigators noted that the oral administration of TKIs may have contributed to higher pharmacy costs, whereas intravenously administered IO agents may have contributed to higher medical costs.

References

1. Shah NJ, Wang CYJ, Rane PP, et al. Real-world treatment patterns, healthcare resource utilization (HCRU) and costs in first-line (1L) advanced renal cell carcinoma (aRCC) in the US. Poster presented at: Kidney Cancer Research Summit; July 23-24, 2026; Boston, MA.
2. Shah N, Wang CY, Rane P, et al. Real-world treatment patterns, healthcare resource utilization (HCRU) and costs in first-line (1L) advanced renal cell carcinoma (aRCC) in the US. Oncologist. 2026;31(suppl 3):029. https://doi.org/10.1093/oncolo/oyag312.029